Combining PARP inhibition and immune checkpoint blockade in ovarian cancer patients: a new perspective on the horizon?

L Musacchio; C M Cicala; F Camarda; V Ghizzoni; E Giudice; M V Carbone; C Ricci; M T Perri; F Tronconi; M Gentile; V Salutari; G Scambia; D Lorusso

doi:10.1016/j.esmoop.2022.100536

Combining PARP inhibition and immune checkpoint blockade in ovarian cancer patients: a new perspective on the horizon?

ESMO Open. 2022 Aug;7(4):100536. doi: 10.1016/j.esmoop.2022.100536. Epub 2022 Jul 15.

Authors

L Musacchio¹, C M Cicala², F Camarda³, V Ghizzoni⁴, E Giudice⁴, M V Carbone⁴, C Ricci⁴, M T Perri⁴, F Tronconi⁵, M Gentile⁶, V Salutari⁴, G Scambia⁷, D Lorusso⁸

Affiliations

¹ Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. Electronic address: https://twitter.com/lucia_musacchio.
² Department of Medical and Surgical Science, Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. Electronic address: https://twitter.com/carlomcicala.
³ Department of Medical and Surgical Science, Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. Electronic address: https://twitter.com/florianacamarda.
⁴ Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁵ Medical Oncology Unit, Marche Polytechnic University, Ancona, Italy.
⁶ Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy.
⁷ Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Life Science and Public Health, Catholic University of Sacred Heart Largo Agostino Gemelli, Rome, Italy.
⁸ Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Life Science and Public Health, Catholic University of Sacred Heart Largo Agostino Gemelli, Rome, Italy. Electronic address: [email protected].

Abstract

Immune checkpoint inhibitors (ICIs) have completely reshaped the treatment of many malignancies, with remarkable improvements in survival outcomes. In ovarian cancer (OC), however, this emerging class of drugs has not yet found a favorable use due to results from phase I and II studies, which have not suggested a substantial antitumoral activity of these agents when administered as monotherapy. Robust preclinical data seem to suggest that the combination ICIs with poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) may result in a synergistic activity; furthermore, data from phase II clinical studies, evaluating this combination, have shown encouraging outcomes especially for those OC patients not suitable for platinum retreatment. While waiting for ongoing phase III clinical trial results, which will clarify the role of ICIs in combination with PARPis in the newly diagnosed OC, this review aims to summarize the preclinical data and clinical evidence available to date.

Keywords: PARP inhibitors; immune checkpoint inhibitors; immunotherapy; ovarian cancer.

Publication types

Review

MeSH terms

Female
Humans
Immune Checkpoint Inhibitors
Ovarian Neoplasms*
Poly(ADP-ribose) Polymerase Inhibitors*

Substances

Immune Checkpoint Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors